The aims of this MBRS Associate Investigator application are to provide training in psychopharmacology, behavioral neuroscience, and receptor pharmacology for undergraduate and graduate minority students. Research support is provided by National Institute on Drug Abuse grants R01DA03796 (Behavioral pharmacology of opioid tolerance) and K02 DA00132 (Behavioral pharmacology of tolerance processes). These projects use drug discrimination assays to assess how pharmacological and behavioral factors modulate development of tolerance to discriminative effects of mu opioids, with particular attention to patterns of tolerance and cross-tolerance among opioids that differ in relative intrinsic efficacy. The goal of MBRS research training in my laboratory is to provide specialized instruction in the design, execution, and analysis of research projects in the area of opioid behavioral pharmacology. The first project in which MBRS trainees will participate examines the role of agonist efficacy in patterns of tolerance and cross-tolerance to the morphine-like discriminative stimulus effects of mu opioids. Experiments will examine tolerance to mu agonists during treatment with a several doses of morphine, tolerance to the same compounds during treatment with the low efficacy mu agonist nalbuphine, and tolerance during treatment with the high efficacy agonist fentanyl. A second project will examine the stimulus effects of opioids in opioid- dependent subjects. A third project, which will serve as the Ph.D. dissertation project for MBRS trainee Tonia Richardson, will use irreversible opioid receptor antagonists to independent test the hypothesis that differences in tolerance are related to differences in agonist intrinsic efficacy. A fourth project will study stimulus effects of low efficacy agonists per se. by establishing representative compounds as discriminative stimuli and examining patterns of generalization and cross- tolerance. A final project will examine whether up-regulation of opioid binding sites is followed by differential changes in stimulus effects of lower and higher efficacy agonists. In addition to conducting individual research projects, MBRS students will attend regular laboratory meetings and seminars in behavioral science and psychopharmacology, and will be encouraged to participate in semi-annual two-day research meetings held with members of neighboring behavioral pharmacology research laboratories and to present their results at national research meetings.